We intend to study the molecular events preceding the polymerization of Hemoglobin S, by osmometry, light scattering and column chromatography, to establish if the phenomenon is concerted on the result of stepwise aggregation. We will study the structural-functional relationship of Hb Beth Israel (beta 102Asn yields Ser), a low affinity hemoglobin associated with clinically apparent cyanosis. We will study the ingress and egress of O2 from reversible and irreversible sickle cells to study the effect of membranes and intracellular polymerization on the red cell transport of O2. BIBLIOGRAPHIC REFERENCES: Fung, L.W.M., Ho, C., Roth, E.F. and Nagel, R.L. The alkylation of hemoglobin S by nitrogen mustard. II. High-resolution proton nuclear magnetic resonance studies. J. Biol. Chem. 250:4786, 1975. Roth, E.F., Jr., Elbaum, D. and Nagel, R.L. Observations in the mechanical precipitation of oxy Hb S and other mutants. Blood 45:377, 1975.